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M A Allen

Publications and source records attributed to M A Allen.

At least 19 recordsLinked to original sources

Analysis of intergenic spacer region length polymorphisms to investigate the halophilic archaeal diversity of stromatolites and microbial mats.

Hamelin Pool in Western Australia is one of the two major sites in the world with active marine stromatolite formation. Surrounded by living smooth and pustular mats, these ancient laminated structures are associated with cyanobacterial communities. Recent studies have identified a wide diversity of bacteria and archaea in this habitat. By understanding and evaluating the microbial diversity of this environment we can obtain insights into the formation of early life on Earth, as stromatolites have been dated in the geological record as far back as 3.5 billion years. Automated ribosomal intergenic spacer analysis (ARISA) patterns were shown to be a useful method to genetically discriminate halophilic archaea within this environment. Patterns of known halophilic archaea are consistent, by replicate analysis, and the halophilic strains isolated from stromatolites have novel intergenic spacer profiles. ARISA-PCR, performed directly on extracted DNA from different sample sites, provided significant insights into the extent of previous unknown diversity of halophilic archaea within this environment. Cloning and sequence analysis of the spacer regions obtained from stromatolites confirmed the novel and broad diversity of halophilic archaea in this environment.

Archaea↗

Adrenomedullin microinjection into the area postrema increases blood pressure.

Adrenomedullin (ADM) circulates in the blood at concentrations comparable to other vasoactive peptides with established roles in cardiovascular regulation. Intravenously administered ADM produces a clear hypotensive effect, whereas intracerebroventricular microinjections result in increases in blood pressure (BP). Recently, we demonstrated that ADM influences neurons of the area postrema (AP), a central nervous system site implicated in cardiovascular control. However, to address directly the physiological significance of the actions of ADM at the AP, an in vivo microinjection study was undertaken. ADM, at two concentrations (1 and 10 microM), in volumes of 50, 100, and 200 nl, was microinjected into the AP or NTS of 21 urethan-anesthetized male Sprague-Dawley rats. Microinjection of 10 microM ADM (100 nl) resulted in significant transient (2-5 min) increases in BP [120 s area under the curve (AUC): 684.3 +/- 268.6 mmHg/s (P < 0.05)], and heart rate (HR) [AUC: 12.5 +/- 4.5 beats/min (P < 0.05)]. The lower concentration of ADM (1 microM) had no effect on either BP (179.1 +/- 143.6 mmHg/s) or HR (0.8 +/- 2.6 beats/min). ADM was also microinjected into the immediately adjacent nucleus of the solitary tract, where it was found to be without effect on either BP or HR. This study demonstrates, for the first time, a physiological role for ADM acting at a specific brain site, the AP, to produce significant cardiovascular responses.

Adrenomedullin↗

In vitro recordings from area postrema neurons demonstrate responsiveness to adrenomedullin.

Adrenomedullin (ADM) is a recently discovered 52-amino acid peptide that exerts potent vasodilatory effects in the periphery and influences the control of body fluid balance when injected centrally. In this study extracellular single-unit recordings were obtained from 94 AP neurons in rat brain slices. Bath application of ADM (10(-7) M) excited 47% (32 of 68) of cells tested, and these effects were found to be dose dependent from 10(-7) to 10(-9) M. Excitation was maintained during synaptic blockade in a low-Ca2+ artificial cerebrospinal fluid solution, demonstrating direct actions of ADM on these neurons. The remaining cells were either unaffected (n = 25) or inhibited (n = 11) by ADM. ADM (10(-7) M) also influenced the spontaneous activity of 9 (7 inhibited, 2 excited) of 16 neurons located in the nucleus tractus solitarii (NTS). However, these effects could be eliminated during synaptic blockade, suggesting indirect actions of the peptide on NTS neurons. These data demonstrate that a specific population of CNS neurons within the AP are directly influenced by ADM and suggest that ADM may exert its effects on the central control of fluid balance through direct actions at this circumventricular organ.

Adrenomedullin↗

Tuberculosis: the other epidemic.

In 1990, the number of cases of tuberculosis (TB) reported in the United States rose 6%. This is a noticeable change since, in prior years, TB had been declining. The increased incidence of TB is largely related to the HIV epidemic. TB is of particular interest in HIV-related illnesses, since it is preventable and treatable. The presentation of HIV-associated TB is different from "standard TB." Nurses need to be informed about the clinical presentation of the disease, the procedures to diagnose it, the treatments, and their potential side effects.

Antitubercular Agents↗

Novel pentamidine analogs in the treatment of experimental Pneumocystis carinii pneumonia.

We have recently demonstrated that substitution of imidazoline moieties for the amidine groups of pentamidine produces a molecule that is effective against rat Pneumocystis carinii pneumonia and that is apparently less toxic than pentamidine. For this reason, 10 novel imidazoline substituted compounds were evaluated for their effect against rat P. carinii pneumonia. While several of the new compounds were observed to have advantages over pentamidine in the treatment of disease in the rat model, only one compound stood out as a potential new clinical agent. Treatment for 2 weeks with intravenous (i.v.) doses of 1,3-di(4-imidazolino-2-methoxyphenoxy)propane (DIMP) at 1 mg/kg per day produced an anti-P. carinii pneumonia effect equivalent to i.v. doses of pentamidine at 10 mg/kg per day. Although pentamidine and one of the test drugs, 1,3-di(4-imidazolinophenoxy)propane, showed no activity against P. carinii pneumonia when administered per os, DIMP exhibited potent anti-P. carinii pneumonia activity when given by daily gavage doses of 40 and 25 mg/kg. DIMP retained significant activity when given every other day by a gavage dose of 25 mg/kg. No toxicity was observed with the drug at any of the dose levels or by either of the routes of administration. However, the low solubility of the drug prevented testing at higher i.v. doses. Our conclusion is that DIMP has the potential of providing a safer and more effective alternative to pentamidine for the treatment of P. carinii pneumonia.

Animals↗

Structure-activity relationships of analogs of pentamidine against Plasmodium falciparum and Leishmania mexicana amazonensis.

The antiprotozoal compound 1,5-di(4-amidinophenoxy)pentane (pentamidine) and 36 of its analogs were screened for in vitro activity against Leishmania mexicana amazonensis clone 669 C4S (MHOM/BR/73/M2269) and Plasmodium falciparum clones W2 (Indochina III/CDC) and D6 (Sierra Leone I/CDC). Pentamidine and each of the analogs tested exhibited activity in vitro against L. m. amazonensis and P. falciparum. The pentamidine analogs were more effective against the P. falciparum clones than against L. m. amazonensis. P. falciparum was extremely susceptible to these compounds, with 50% inhibitory concentrations as low as 0.03 microM. While none of the analogs exhibited marked improvement in antileishmanial activity compared with pentamidine, 12 of the pentamidine analogs showed activity approximately equal to or greater than that of the parent compound. From the promising activity exhibited by the pentamidine analogs in this in vitro study and their potential for reduced toxicity relative to the parent drug, pentamidine-related compounds hold promise as new agents for the treatment of protozoal infections.

Animals↗

Experiences with anaerobes.

Anaerobiology has long been an underdeveloped entity in the routine clinical microbiology laboratory. The difficulties and successes in setting up this specialist department in such a laboratory are outlined. It is concluded that specimen quality, technical expertise, taxonomy and identification remain the areas which need most attention.

Bacteria, Anaerobic↗

CA 125 as a tumour marker in epithelial ovarian cancer.

CA 125, a high molecular weight glycoprotein, was measured in sera from patients with epithelial ovarian cancer, patients with benign gynaecological disease and in patients with non-ovarian adenocarcinomas. High levels (greater than 35 U/ml) were found in 48/50 patients with active ovarian cancer but in only 3/26 patients who had an ovarian cancer previously diagnosed but who were apparently disease free. 6/23 patients with non-ovarian adenocarcinomas as well as 4/18 patients with benign gynaecological disease also had elevated levels. CA 125 levels were higher in serious than non-serous ovarian cancers and tended to increase with increasing stage. In all of 19 patients with ovarian cancer who responded to treatment CA 125 levels fell while 17/20 with progressive disease showed a rise. In 7/8 patients, serial determination of CA 125 showed a rise before the clinical detection of recurrence, the median lead-time being 3.5 months. We conclude that CA 125 is an excellent marker in the management of patients with epithelial ovarian cancers.

Antigens, Tumor-Associated, Carbohydrate↗

Baroreceptor responses derived from a fundamental concept.

A model is presented that relates the change in baroreceptor firing rate to a step change in blood pressure. This relationship is nonlinear since the alteration in rate of firing depends on the current rate of firing. It is shown that this simple relationship embodies all currently established baroreceptor response modes. The model needs refinement to allow for effects arising from the properties of the tissue matrix in which the receptors are embedded. Further analysis is precluded at present owing to paucity of quantitative experimental data.

Animals↗

CEA-like material in cytosols from human breast carcinomas. Correlation with biochemical and pathologic parameters.

CEA-like material was found in 51 of 62 primary human breast carcinomas and in only 2 of 12 fibroadenomas. Levels of carcinoma CEA-like material correlated weakly with cytoplasmic estradiol receptor levels, total cytosol estrogens, and cytosol progesterone. Levels of CEA-like material showed no significant correlation with carcinoma stage, grade, cellularity, size or histologic type. Levels, however, correlated inversely with lymphocyte infiltration.

Adenofibroma↗

Chemical stability of prostacyclin (PGI2) in aqueous solutions.

The rate constant for the hydrolysis of prostacyclin (PGI2) to 6-keto-PGF1alpha was measured by monitoring the UV spectral change, over a pH range 6 to 10 at 25 degrees C and the total ionic strength of 0.5 M. The first-order rate constant (kdegreesobs) extrapolated to zero buffer concentration follows an expression, kdegreesobs = kH+ (H+), where kH+ is a second-order rate constant for the specific acid catalyzed hydrolysis. The value of kH+ obtained (3.71 x 10(4) sec-1 M-1) Is estimated approximately 700-fold greater than a kH+ value expected from the hydrolysis of other vinyl ethers. Such an unusually high reactivity of PGI2 even for a vinyl ether is attributed to a possible ring strain release that would occur upon the rate controlling protonation of C5. A Brønsted slope (alpha) of 0.71 was obtained for the acid (including H3O+) catalytic constants, from which a pH independent first-order rate constant for the spontaneous hydrolysis (catalyzed by H2O as a general acid) was estimated to be 1.3 x 10(-6) sec-1. An apparent activation energy (Ea) of 11.85 Kcal/mole was obtained for the hydrolysis at pH 7.48, from which a half-life of PGI2 at 4 degrees C was estimated to be approximately 14.5 min. when the total phosphate concentration is 0.165 M (cf. 3.5 min. at 25 degrees C).

Buffers↗

A study of the mechanism of transport of benzylpenicillin in the rat submaxillary gland.

In vitro studies performed on slices of rat submaxillary gland to evaluate uptake and efflux of 14C-benzylpenicillin (10(-6)M, 10(-5)M) showed that uptake of 14C-benzylpenicillin was not significantly altered by aeration with N2, addition of 10(-5)M CN- or 10(-3) M probenecid, or substitution of K2SO4 in place of NaCl in the KRT buffer to produce a depolarizing solution. Lowering the extracellular pH (pHe) resulted in increases rates of uptake and efflux, whereas increasing the pHe resulted in decreased rates. The in vivo uptake of penicillin into whole glands excised from rates treated in vivo was very similar to that seen in the slice preparation. However, addition of probenecid to salivary gland slices in vitro decreased the rate of effux. These data suggest that the movement of penicillin in the rat salivary gland may occur by a two-step mechanism: (1) passive exchange of penicillin into the gland dependent on the degree of dissociation of penicillin, and (2) active excretion of the drug from the gland by a transport mechanism similar to that of the kidney densitive to probenecid.

Animals↗

Effects of bis(2-ethylhexyl) phthalate on chromosomes of human leukocytes and human fetal lung cells.

Blood from two male and two female donors was exposed at 37degrees for 4 hr to concentrations of 60.0, 6.0, 0.6, and 0.06 mug of a widely used plasticizer, bis (2-ethylhexyl) phthalate, per milliliter of blood. The bis(2-ethylhexyl) phthalate was solubilized with polysorbate 80. Appropriate polysorbate and nonpolysorbate controls also were established. Following the 4 hr of incubation, phytohemagglutinin was added and tissue cultures were established. In addition, human fetal lung cells were exposed in tissue culture to a medium containing 6.0 mug/ml of bis(2-ethylhexyl) phthalate in polysorbate 80 for 5 days. Similar controls also were established for these experiments. Analysis of chromosome preparations from all cultures obtained failed to show any increased evidence of isochromatid and chromatid breaks or gaps or abnormal forms at any studied concentration when compared to the control cultures. In addition, analysis of fetal lung cell preparations for aneuploidy failed to reveal any differences between cells from study and control cultures. This study involved a short-term exposure to bis(2-ethylhexyl) phthalate in various concentrations which did not cause damage in leukocytes or fetal lung cells.

Cells, Cultured↗